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Barbara J. Weiland, Ph.D., now of the University of Colorado, Boulder, used her 2012 NARSAD Young Investigator Grant to study substance abuse in young people and identify whether—and how—brain structure abnormalities might play a role in the development of substance use disorders (SUD).

The new study probed the key questions: Are structural abnormalities in the brain present in young people at high risk to develop substance-abuse disorders, or if there are abnormalities present, are they a result of substance abuse? Also, are these structures related to “externalizing” behaviors, such as aggression or delinquency?

Dr. Weiland worked with colleagues at the University of Michigan who included Jon-Kar Zubieta, M.D., Ph.D.,—former NARSAD Young and Independent Investigator Grantee and current NARSAD Distinguished Investigator Grantee—to study a sample of 106 young people aged 18 to 23, 42 of whom were considered at early risk of substance abuse. This determination was made on the basis of early onset of substance use.

Based on high-resolution brain scans made of all the young people enrolled in the study, the team found that when compared with 64 youth of the same age not considered at high risk, the early risk group, as expected, had smaller volumes of certain brain structures. “While family history is a powerful predictor of later SUD, it’s likely that there are neurobiological contributions,” Dr. Weiland and the team noted in reporting their results in Drug and Alcohol Dependence, April 1st.

Specifically, two parts of the brain, the left frontal cortex, and in particular the left superior frontal cortex—both involved in the control of behavior—were smaller in the early risk group even when controlling for lifetime alcohol and cigarette use. Similar findings have been shown in past studies of young people who had early-onset substance abuse and/or had a family history of alcohol abuse.

The new work shows these structural deficiencies are present even when excluding subjects who had already started abusing alcohol or nicotine. This “supports the tentative conclusion that they [the specific reductions noted in brain volume] represent a pre-existing vulnerability factor.” In other words, they seem to contribute to a person’s inherent risk for substance abuse, rather than being a product of the early abuse. The team acknowledges the cause-effect question is highly complex and calls for long-term longitudinal studies to learn more.

Article comments

Thank you Dr Weiland for you fine work. In my neuropsychological assessment of over 9000 patients I find that left frontal dysfunction is involved in bipolar disorder and schizophrenia as well as substance abuse.

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